In the US, 10% of couples have medical appointments related to infertility with 40% of infertility being associated with the male. Globally, this translates to over 73 million infertile couples. Typical male reproductive health exams assess sperm number, appearance, and motility. Unfortunately, half of infertile men have sperm that meet normal parameters for these descriptive criteria and are only identified as having “idiopathic infertility” after repeatedly failing at both natural conception and techniques of assisted reproduction such as intra-uterine insemination (IUI). Because each failed cycle inflicts great physical, emotional, and financial tolls on couples and it costs the US healthcare system over $5 billion annually, there is a tremendous need for a practical test of sperm function. Data on sperm function would allow clinicians to direct their patients toward a technology of assisted reproduction that would give them the best chance to conceive.
Upon entrance into the female tract, sperm are not immediately able to fertilize an egg. Rather, they must undergo a process of functional maturation known as “capacitation.” This process relies upon their ability to respond to specific stimuli by having specific changes in their cell membrane, namely a change in the distribution pattern of the ganglioside GM1 in response to exposure to stimuli for capacitation.
Various GM1 localization patterns have been identified and associated with capacitation or non-capacitation. In particular, apical acrosome (AA) GM1 localization patterns and acrosomal plasma membrane (APM) GM1 localization patterns have been associated with capacitation in bovine and human sperm. Sperm capacitation can be quantitatively expressed as a Cap-Score™ value, generated via the Cap-Score™ Sperm Function Test (“Cap-Score™ Test” or “Cap-Score”), is defined as ([number of apical acrosome (AA) GM1 localization patterns+number of acrosomal plasma membrane (APM) GM1 localization patterns]/total number of GM1 labeled localization patterns) where the number of each localization pattern is measured and then ultimately converted to a percentage score. In addition to APM GM1 localization patterns and AA GM1 localization patterns, the other labeled localization patterns included Lined-Cell GM1 localization patterns, intermediate (INTER) GM1 localization patterns, post acrosomal plasma membrane (PAPM) GM1 localization patterns, apical acrosome/post acrosome (AA/PA) GM1 localization patterns, equatorial segment (ES) GM1 localization patterns, and diffuse (DIFF) GM1 localization patterns. (Travis et al., “Impacts of common semen handling methods on sperm function,” The Journal of Urology, 195 (4), e909 (2016)).